Phase 2 Randomized Bivalent RSVpreF Maternal Vaccine Trial: Final Safety, Antibody Persistence and Efficacy

Abstract

BACKGROUND: This report summarizes the final results from a randomized, placebo-controlled, phase 2b trial evaluating safety, antibody persistence, and potential efficacy of a bivalent respiratory syncytial virus (RSV) prefusion F (RSVpreF) vaccine in pregnant individuals and their infants. METHODS: Maternal participants were randomized from 24-36 weeks gestation to receive RSVpreF (120 or 240 µg ± aluminum hydroxide) or placebo. RESULTS: This analysis included 579 pregnant individuals and 572 infants from 4 countries (Argentina, Chile, South Africa, United States); 462 maternal participants received RSVpreF. Adverse events in the month following vaccination (maternal) or birth (infant) were mostly anticipated events in pregnancy and the neonatal period, respectively. For all RSVpreF groups, combined RSV-A/-B 50% neutralizing titers peaked 2 weeks after vaccination. At delivery, geometric mean titer ratios between RSVpreF and placebo recipients' infants were 10.9-13.6. Transplacental transfer ratios (all groups) were 1.39-1.83. Neutralizing geometric mean titers remained higher in infants whose mothers received RSVpreF versus placebo through their first 6 months of life, with an estimated half-life of 39-44 days. In an exploratory analysis, observed efficacy (95% confidence interval) for the combined RSVpreF groups against medically attended and severe medically attended infant RSV lower respiratory tract illness through the first 180 days of life was 75% (-11%, 94%) and 83% (-48%, 99%), respectively. CONCLUSIONS: RSVpreF had a favorable safety profile and elicited robust neutralizing responses with efficient transplacental transfer. The potential to prevent infant RSV-associated lower respiratory tract illness was subsequently confirmed in the pivotal phase 3 efficacy trial. (NCT04032093).